History Of Non-melanoma Skin Cancer Research Articles

Risk of a Second Primary Cancer after Non-melanoma Skin Cancer in White Men and Women: A Prospective Cohort Study

Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer at other sites. The purpose of this study is to prospectively examine the risk of primary cancer according to personal history of NMSC. In two large US cohorts, the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS), we prospectively investigated this association in self-identified white men and women. In the HPFS, we followed 46,237 men from June 1986 to June 2008 (833,496 person-years). In the NHS, we followed 107,339 women from June 1984 to June 2008 (2,116,178 person-years). We documented 29,447 incident cancer cases other than NMSC. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs). A personal history of NMSC was significantly associated with a higher risk of other primary cancers excluding melanoma in men (RR=1.11; 95% CI 1.05-1.18), and in women (RR=1.20; 95% CI 1.15-1.25). Age-standardized absolute risk (AR) was 176 in men and 182 in women per 100,000 person-years. For individual cancer sites, after the Bonferroni correction for multiple comparisons (n=28), in men, a personal history of NMSC was significantly associated with an increased risk of melanoma (RR=1.99, AR=116 per 100,000 person-years). In women, a personal history of NMSC was significantly associated with an increased risk of breast (RR=1.19, AR=87 per 100,000 person-years), lung (RR=1.32, AR=22 per 100,000 person-years), and melanoma (RR=2.58, AR=79 per 100,000 person-years). This prospective study found a modestly increased risk of subsequent malignancies among individuals with a history of NMSC, specifically breast and lung cancer in women and melanoma in both men and women.

Update on the Epidemiology of Melanoma

Cutaneous malignant melanoma (CMM) has been increasing steadily in incidence over the past 30 years. Recent studies have explored associations between CMM and varying physiologic risk factors, such as nevi or hair and eye color, in addition to historical features such as a personal history of nonmelanoma skin cancer (NMSC), childhood cancers, Parkinson's Disease, hormone exposure and family history of CMM. Genome-wide association studies have also uncovered many genetic determinants of CMM risk. Ultimately, ultraviolet (UV) radiation exposure remains the most important modifiable risk factor for CMM. Organ transplant recipients, and nonsteroidal anti-inflammatory usage may also play a role. While risk factors are important to identify, effective campaigns to reduce the burden of disease through early detection and prevention are essential. We present detailed data regarding these facets of care for the CMM patient, and provide an update on the epidemiology of CMM.

Weight Status, Physical Activity and the Associations with Health Related Physical Fitness in Nine to Twelve Year Old Scottish Children

OBJECTIVE: To develop a self-assessed melanoma risk score to identify high-risk persons for screening METHODS: We used data from a 1997 melanoma case-control study from Washington State, USA, where 386 cases with invasive cutaneous melanoma and 727 controls were interviewed by telephone. A logistic regression prediction model was developed on 75% of the data and validated in the remaining 25% by calculating the area under the receiver operating characteristic curve (AUC), a measure of predictive accuracy from 0.5-1 (higher scores indicating better prediction). A risk score was calculated for each individual, and sensitivities for various risk cutoffs were calculated. RESULTS: The final model included sex, age, hair color, density of freckles, number of severe sunburns in childhood and adolescence, number of raised moles on the arms, and history of non-melanoma skin cancer. The area under the receiver operating characteristic curve(AUC) was 0.70 (95% CI: 0.64, 0.77). The top 15% risk group included 50% of melanomas (sensitivity 50%). CONCLUSIONS: This self-assessed score could be used as part of a comprehensive melanoma screening and public education program to identify high-risk individuals in the general population. This study suggests it may be possible to capture a large proportion of melanomas by screening a small high-risk group. Further study is needed to determine the costs, feasibility, and risks of this approach.

Predictors of Basal Cell Carcinoma in High-Risk Patients in the VATTC (VA Topical Tretinoin Chemoprevention) Trial

Basal cell carcinoma (BCC) is the most common cancer in the United States today, and patients who have had one are likely to have multiple carcinomas over time. Predictors of new BCCs on the face and ears among those at very high risk have not been studied in detail. We sought to do so prospectively in the context of a 6-year trial. We found that the number of BCCs in the prior 5 years was the most important predictor. Age, sun sensitivity, occupational sun exposure before the age of 30 years (but not afterward), lower educational level, history of eczema, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and more sunscreen use in the week, but not the 6 months, before enrollment were also independent predictors, but sunburns, baseline sun exposure, and other sun-protective measures, other skin cancers, and actinic keratoses were not. None of the eczema patients had a history of topical calcineurin use. The cumulative risk of BCC was 55% at 5 years. These findings document the key risk factors in this very high-risk population, suggesting that the history of eczema may increase the risk in those at high risk and that early sun exposure is important even in this group, and underscoring the need for chemopreventive strategies.

Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features

Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC). A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001). The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001). Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC) compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.

Nonmelanoma Skin Cancers Among HIV-Infected Persons in the HAART Era

Nonmelanoma Skin Cancers Among HIV-Infected Persons in the HAART Era

A population-based study of DNA repair gene variants in relation to non-melanoma skin cancer as a marker of a cancer-prone phenotype.

For unknown reasons, non-melanoma skin cancer (NMSC) is associated with increased risk of other malignancies. Focusing solely on DNA repair or DNA repair-related genes, this study tested the hypothesis that DNA repair gene variants contribute to the increased cancer risk associated with a personal history of NMSC. From the parent CLUE II cohort study, established in 1989 in Washington County, MD, the study consisted of a cancer-free control group (n 5 2296) compared with three mutually exclusive groups of cancer cases ascertained through 2007: (i) Other (non-NMSC) cancer only (n 5 2349); (ii) NMSC only (n 5 694) and (iii) NMSC plus other cancer (n 5 577). The frequency of minor alleles in 759 DNA repair gene single nucleotide polymorphisms (SNPs) was compared in these four groups. Comparing those with both NMSC and other cancer versus those with no cancer, 10 SNPs had allelic trend P-values <0.01. The two top-ranked SNPs were both within the thymine DNA glycosylase gene (TDG). One was a non-synonymous coding SNP (rs2888805) [per allele odds ratio (OR) 1.40, 95% confidence interval (CI) 1.16-1.70; P-value 5 0.0006] and the other was an intronic SNP in high linkage disequilibrium with rs2888805 (rs4135150). None of the associations had a P-value <6.6310(-5), the threshold for statistical significance after correcting for multiple comparisons. The results pinpoint DNA repair genes most likely to contribute to the NMSC cancer-prone phenotype. A promising lead is genetic variants in TDG, important not only in base excision repair but also in regulating the epigenome and gene expression, which may contribute to the NMSC-associated increase in overall cancer risk.

Randomized Controlled Trial of Sirolimus for Renal Transplant Recipients at High Risk for Nonmelanoma Skin Cancer

Sirolimus has antineoplastic effects and may reduce skin cancer rates in kidney transplant patients. This prospective, multicenter, randomized, open-label, controlled trial randomized 86 kidney transplant recipients (≥1 year posttransplant) with history of nonmelanoma skin cancer (NMSC) to continue calcineurin inhibitor (CNI) or convert to sirolimus. Patients were stratified by number of NMSC lesions (0-5, 6-20) in previous year. Primary end point was number of biopsy-confirmed new NMSC lesions per patient-year. Yearly NMSC rate was significantly lower with sirolimus (1.31 vs. 2.48 lesions/patient-year; p = 0.022). Squamous cell carcinoma occurred at a lower rate in the sirolimus versus CNI group (p = 0.038); basal cell carcinoma rate was similar in both. A lower proportion of patients receiving sirolimus developed new or recurrent NMSC (56.4% vs. 80.9%; p = 0.015) or new squamous cell carcinoma (41.0% vs. 70.2%; p = 0.006). No sirolimus patients and one CNI continuation patient experienced acute rejection. Incidence of treatment-emergent adverse events was similar between groups; however, discontinuation rates related to adverse events were significantly higher with sirolimus (46.2% vs. 0%; p < 0.001). In kidney transplant recipients with history of NMSC, conversion from CNI to sirolimus reduced rates of NMSC, without increasing acute rejection risk.

Abstract 636: Non-melanoma skin cancer and risk of second primary cancer

Abstract Objective: Previous studies suggest a positive association between history of non-melanoma skin cancer (NMSC) and risk of subsequent cancer development. We prospectively investigate this association in both men and women. Methods: In two large cohorts in the US, the Health Professionals Follow-up Study (HPFS) and the Nurses’ Health Study (NHS), we prospectively examined the risks of primary cancer according to history of NMSC. In the HPFS, 876,094 person-years were followed up from June 1986 to June 2008. In the NHS, 2,358,185 person-years were followed up from June 1984 to June 2008. We documented 30,636 cancer cases after ongoing NMSC diagnosis. The median time (and range) of diagnosis between NMSC and subsequent cancer was 156 (3 - 342) months in the NHS, and 116 (3 - 259) months in the HPFS. Cox proportional hazard models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusting for major cancer risk factors (e.g. age, smoking, body mass index, physical activity, etc). Results: A history of NMSC was associated with a higher risk of other primary cancers in men (RR = 1.15; 95% CI: 1.08, 1.21; P &amp;lt; 0.0001), and in women (RR = 1.25; 95% CI: 1.20, 1.31; P &amp;lt; 0.0001). For individual cancer sites, in men, a history of NMSC was associated with an increased risk of prostate cancer, non-Hodgkin lymphoma, and melanoma. In women, a history of NMSC was associated with an increased risk of breast cancer, endometrial cancer, ovarian cancer, lung cancer, non-Hodgkin lymphoma, renal cancer, melanoma, and oral cancer. Conclusions: Our prospective-cohort study provides evidence for an association between a history of NMSC and an increased risk of subsequent malignancies. Further studies are warranted to identify the potential mechanism underlying this relationship. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 636. doi:1538-7445.AM2012-636

Abstract 2636: Nonmelanoma skin cancer as a marker of a cancer-prone phenotype: Potential role of DNA repair gene variants

Abstract Purpose: For unknown reasons, nonmelanoma skin cancer (NMSC) is associated with increased risk of other malignancies. This study tested the hypothesis that DNA repair gene variants contribute to the increased cancer risk associated with a personal history of NMSC. Methods: From the parent CLUE II cohort study, established in 1989 in Washington County MD, the study consisted of a cancer-free control group (n=2,296) compared to three mutually exclusive groups of cancer cases ascertained through 2007: 1) Other (non-NMSC) cancer only (n=2,349); 2) NMSC only (n=694); and 3) NMSC plus other cancer (n=577). The frequency of minor alleles in 759 DNA repair single nucleotide polymorphisms (SNPs) was compared in these four groups. Results: Comparing those with both NMSC and other cancer versus those with no cancer, 10 SNPs had additive model p-values&amp;lt;0.01. The two top-ranked SNPs were both within the thymine DNA glycosylase gene (TDG). One was a nonsynonymous coding SNP (rs2888805) (per allele odds ratio (OR) 1.40, 95% confidence interval (CI) 1.16-1.70; p-value=0.0006) and the other was an intronic SNP in high linkage disequilibrium with rs2888805 (rs4135150). Conclusion: The results pinpoint DNA repair genes most likely to contribute to the NMSC cancer-prone phenotype. A promising lead is genetic variants in TDG, important not only in base excision repair but also in regulating the epigenome and gene expression, which may contribute to the NMSC-associated increase in overall cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2636. doi:1538-7445.AM2012-2636

Risk of second cancers after the diagnosis of non‐melanoma skin cancer in Korean patients

Individuals with a personal history of non-melanoma skin cancer (NMSC) are known to have an increased risk of subsequent cancers. However, most of the studies regarding this fact were done on Caucasian populations. We investigated whether Korean patients with NMSC have an increased risk of developing second cancers compared to the general Korean population. Five hundred and thirty-two patients diagnosed with NMSC at the Department of Dermatology of Yonsei University Health System from 1999 to 2008 were assessed for development of second cancers. The overall second cancer incidence was increased among patients diagnosed with NMSC compared with the general population in Korea: 37 second cancer total (standardized incidence ratio [SIR] 1.38, 95% confidence interval [CI] 1.10-1.90); 23 second cancers in males (SIR 4.24, 95% CI 2.69-6.36); and 14 second cancers in females (SIR 2.28, 95% CI 1.25-3.83). There were significantly increased incidence ratios for NMSC (eight second cancers [SIR 9.52, 95% CI 4.11-18.77]), bladder cancer (four second cancers [SIR 4.21, 95% CI 1.15-10.78]) and nasopharyngeal cancer (one second cancer [SIR 20.00, 95% CI: 1.51-25.33]). Korean patients diagnosed with NMSC had more second cancers, particularly other skin cancers. This study provides additional evidence that NMSC may be a clinically significant and substantial risk factor for second cancers even in a Korean population, in which the incidence of NMSC is much lower than Caucasians.

Skin cancer after pancreas transplantation

Skin cancer in patients who have undergone pancreas transplantation (PT) has not been extensively characterized. We sought to describe the incidence, tumor burden, and risk factors for skin cancer in PT recipients at Mayo Clinic from 1998 through 2006. A retrospective study was performed by analyzing outcomes among a cohort of pancreas allograft recipients at Mayo Clinic between 1998 and 2006. Among 216 allogeneic PT recipients at 2, 5, and 10 years posttransplantation, the cumulative incidence of any skin cancer was 4.7%, 12.7%, and 19.6%; the cumulative incidence of squamous cell carcinoma was 2.8%, 10.3%, and 16.7%; and the cumulative incidence of basal cell carcinoma was 2.4%, 7.8%, and 17.4%, respectively. The cumulative incidence of a second squamous cell carcinoma developing was 56% at 2 years; the cumulative incidence of a second basal cell carcinoma developing was 36% at 2 years. Of the risk factors examined, only age and having a skin cancer before transplantation were predictive of skin cancer development. This was a retrospective study. Results from a large tertiary center may not be generalizable. Nonmelanoma skin cancers commonly occur in recipients of PT, and those patients who have a history of nonmelanoma skin cancer have a very high likelihood of further skin cancer development.

Abstract A52: A phase III skin cancer chemoprevention study of DFMO in subjects with a history of non-melanoma skin cancer (NMSC): Follow-up of NMSC events greater than 5 years post-study participation

Abstract The most commonly diagnosed malignancy in the United States is non-melanoma skin cancer (NMSC) with &amp;gt; 2 million new cases of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) predicted for 2010. The economic burden and increasing incidence in younger populations, especially women, reinforces the value of skin cancer prevention. Health education and prior attempts at skin cancer chemoprevention have had limited success. A strong link between epithelial carcinogenesis and elevated polyamines, together with a series of phase I and II trials, led to a NCI-sponsored phase III double-blind, placebo-controlled skin cancer chemoprevention trial of α-difluoromethylornithine (DFMO) (500 mg/m2/day) for 4–5 years in 291 subjects with a history of NMSC. Subjects receiving DFMO developed significantly fewer BCC s than placebo subjects with an event rate of 0.28 BCC/person/year versus 0.40 BCC/person/year, (P = 0.03; Total BCCs: DFMO 163, placebo 243). DFMO appeared to have minimal effects on SCC incidence (DFMO 0.15 SCC/person/year, placebo 0.19, p=0.56; Total SCCs: DFMO 95, placebo 115). Subjects tolerated DFMO well, and the only significant observed toxicity was increased audiometric hearing loss. A key issue in the clinical viability of a chemoprevention agent after acute effectiveness and/or tolerance is the latent effectiveness and/or toxicity of the agent. Such effects attributable to DFMO have not been assessed. Earlier chemoprevention research has observed positive and negative latent effects with chemopreventive agents. Use of tamoxifen (5 years) for breast cancer prevention provided continued or greater protection for up to 10 years after drug stoppage. On the contrary, early work with retinoids in oral cancer prevention implied a rebound effect with subjects developing more neoplasms upon discontinuation. Also, the recent linkage between isotretinoin and inflammatory bowel disease is a concerning example of toxicity experienced years after use of a chronically administered agent. The continued interest in DFMO as a chemopreventive agent provided cause to update the clinical data and overall health status of the 291 subjects from the phase III skin cancer prevention study of DFMO to understand the sustainability of the observed DFMO effects. After institutional review board approval, we reviewed medical records of 243 subjects who received care at UW Health. Individual records were manually reviewed, and a pending comparative review of data mining by Natural Language Processing will also be completed. Both reviews focused on the skin cancer events by histology, other neoplasia (invasive and non-invasive), significant other diagnoses, and survival. The rate of skin cancer recurrence from end of study drug to the time of last medical contact (the primary endpoint) was compared between subjects randomized to DFMO or placebo using a two-sample test for primary analysis. As a secondary analysis, the rate of skin cancer recurrence from randomization to the time of last medical contact was also compared. In an exploratory analysis, the primary endpoint was analyzed using Poisson regression models to account for the baseline patient/disease characteristics at the time of randomization such as sex and age of patients and pre-study skin cancer history. Data from the 243 subjects totaling over 2,300 person years is undergoing further validation and preliminary data analysis, and will be available shortly. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A52.

Seropositivity for human papillomavirus and incidence of subsequent squamous cell and basal cell carcinomas of the skin in patients with a previous nonmelanoma skin cancer

Infection with human papillomaviruses (HPVs) is a risk factor for several epithelial cancers, but its relationship with keratinocyte tumours has not yet been established. Objective In this prospective study we investigated the possible role of different HPVs in the incidence of a subsequent nonmelanoma skin cancer (NMSC). One hundred and fifty-three patients with squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) enrolled in a previous case-control study were re-contacted, and a follow-up visit was offered. Demographic and clinical data, date of first NMSC presentation, Fitzpatrick skin type and history of NMSC during the follow-up period were ascertained. Recurrences and new second cancers were considered together as 'outcomes' in time-to-event analyses and in Cox proportional hazard models. Clinical data were obtained in 107 patients. HPV seropositivity at baseline was strongly associated with the risk of developing a second SCC after 5 years for a number of beta and gamma HPV types. For example, HPV-24-seropositive patients with an SCC at baseline had a 4-fold increased risk of developing a subsequent SCC (hazard ratio 4·35, 95% confidence interval 1·2-15·6, P = 0·024). No association between serological status for any HPV type tested and an increased risk of BCC was found. We observed a consistent pattern of a positive association between seropositivity for beta and gamma HPV types and the risk of a subsequent SCC in patients with a previous SCC. Our data corroborate the results of previous case-control studies and may spur further prospective studies on the causal role of HPVs in NMSC.

Calcium Plus Vitamin D Supplementation and the Risk of Nonmelanoma and Melanoma Skin Cancer: Post Hoc Analyses of the Women's Health Initiative Randomized Controlled Trial

In light of inverse relationships reported in observational studies of vitamin D intake and serum 25-hydroxyvitamin D levels with risk of nonmelanoma skin cancer (NMSC) and melanoma, we evaluated the effects of vitamin D combined with calcium supplementation on skin cancer in a randomized placebo-controlled trial. Postmenopausal women age 50 to 79 years (N = 36,282) enrolled onto the Women's Health Initiative (WHI) calcium/vitamin D clinical trial were randomly assigned to receive 1,000 mg of elemental calcium plus 400 IU of vitamin D3 (CaD) daily or placebo for a mean follow-up period of 7.0 years. NMSC and melanoma skin cancers were ascertained by annual self-report; melanoma skin cancers underwent physician adjudication. Neither incident NMSC nor melanoma rates differed between treatment (hazard ratio [HR], 1.02; 95% CI, 0.95 to 1.07) and placebo groups (HR, 0.86; 95% CI, 0.64 to 1.16). In subgroup analyses, women with history of NMSC assigned to CaD had a reduced risk of melanoma versus those receiving placebo (HR, 0.43; 95% CI, 0.21 to 0.90; P(interaction) = .038), which was not observed in women without history of NMSC. Vitamin D supplementation at a relatively low dose plus calcium did not reduce the overall incidence of NMSC or melanoma. However, in women with history of NMSC, CaD supplementation reduced melanoma risk, suggesting a potential role for calcium and vitamin D supplements in this high-risk group. Results from this post hoc subgroup analysis should be interpreted with caution but warrant additional investigation.

Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels with risk of malignant melanoma

We examined the relationship of insulin-like growth factor-I (IGF-I) and its primary growth factor, IGF binding protein-3 (IGFBP-3) with malignant melanoma using interview data and sera from cases (n = 286) and controls (n = 289) in a population-based case-control study conducted in 1986-1992 on Oahu, Hawaii. Serum IGF-I and IGFBP-3 concentrations were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression and adjusting for age, sex, education, number of blistering sunburns, ability to tan, hair color, energy intake, BMI, height, smoking status, and drinking status. An inverse relationship was found between IGF-I concentration and melanoma (OR for upper vs. lower tertile: 0.44, 95% CI: 0.25-0.79), but clear associations were not observed between malignant melanoma and upper tertiles of IGFBP-3 and the IGF-1/IGFBP-3 molar ratio. The inverse association with IGF-I was strongest among subjects who did not report a history of non-melanoma skin cancer (NMSC) (OR for ≥ vs. < median: 0.39, 95% CI: 0.24-0.65), and a positive association was found among those with such a history (OR: 3.6, 95% CI: 1.0-13; p (interaction) = 0.0035). Our findings observed here between serum IGF-I and malignant melanoma warrants replication in studies with a larger sample size and a prospective design.

Defining fast-growing melanomas

The growth rate (GR) of melanomas is not uniform. A fast-growing subtype has been identified and seems to have a role in the stabilization of the mortality rates because of melanoma. To examine features associated with fast-growing melanomas (FGMs) and to determine the relationship between the GR and well-recognized prognostic factors of melanoma, a series of 386 new invasive cutaneous melanomas seen during 2004-2009 were retrieved from our database. The GR was calculated according to earlier published studies. FGMs were defined as those whose GR was greater than 0.49 mm per month. Differences in clinical, epidemiological, and pathological features were evaluated. Correlations between the GR, tumor thickness, and mitotic rate were also analyzed. FGMs were significantly more prevalent among patients aged over 65 years and with a higher rate of past personal history of nonmelanoma skin cancer. This subtype was over-represented among melanomas located on both nonexposed and usually exposed skin and was less related to earlier sunburns. Patients with FGMs presented with more aggressive pathological features and had more advanced disease with sentinel node analysis affected in up to 35% of cases. There was a strong positive correlation between the GR and tumor thickness (r=0.762), and mitotic rate (r=0.542). This study was limited by being retrospective in nature. FGMs are a highly aggressive subtype of melanomas that seem to develop after at least two routes, one related to chronic sun exposure and another unrelated to the sun. Older patients have a higher predisposition to develop this kind of tumor. This variant warrants specific strategies to improve primary and secondary prevention.

Predicting melanoma risk for the Australian population

As melanoma incidence in Australia continues to rise, targeting high-risk individuals for early detection is of paramount importance. We aimed to design a population-specific risk assessment tool to improve on the use of intuition alone for assignment of surveillance strategies for high-risk individuals and help communicate risk more accurately and effectively to patients. Methods used in the development of breast cancer risk models were adopted. Data from a large meta-analysis was used to determine risk estimates. Attributable risk was calculated for each risk factor using data from the Victorian Melanoma Service. Local prevalence data from state cancer registries was incorporated to estimate 5-year risk of melanoma. Independent risk factors identified were common naevi, atypical naevi, hair colour, freckles, family history of melanoma and personal history of non-melanoma skin cancer. Personal history of melanoma was the strongest risk factor for developing another (relative risk 7.28, 7.24). Absolute risk for individuals varies greatly with age, risk factor profiles and proximity to the equator. We have developed a melanoma risk assessment tool based on the best available information (http://www.victorianmelanomaservice.org/calculator). The tool is easily modified as new information becomes available.

ASIP genetic variants and the number of non-melanoma skin cancers

Patients with primary non-melanoma skin cancers (NMSCs) tend to develop these cancers at multiple independent sites. We examined the genetic factors in the development of multiple NMSCs among Caucasian women with 28 years of follow-up. We initially evaluated 19 SNPs in nine pigmentation genes with the number of NMSCs in 492 cases and 619 controls without a history of NMSC. We found nominal significant associations between two ASIP gene-related SNPs, rs1885120 and rs910873, and an ASIP haplotype (AH) (rs4911414 allele T and rs1015362 allele G) and an increased number of NMSCs, with p-values of 0.008, 0.01, and 0.01, respectively. We further evaluated these two SNPs and AH haplotype in three data sets. In a joint analysis with 1,507 cases and 4,335 controls, AH haplotype was independently associated with the number of NMSCs with odds ratio (OR) (95% confidence interval (CI)) of 1.45(1.25-1.68) (p-value = 6.2E-07). The AH haplotype was associated with an increased risk of developing one NMSC (OR 1.32; 95% CI, 1.07-1.63). The OR increased to 1.45(1.18-1.78) for those with 2-4 NMSCs and 1.84(1.34-2.53) for those with at least five. The findings suggest that ASIP locus is associated with the number of NMSCs.

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

BackgroundPreclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs).MethodsA double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided.ResultsThere was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma skin cancer history, and patient time on study, the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm (RR = 0.41, 95% CI = 0.23 to 0.72, P = .002) as were the numbers of BCCs (RR = 0.40, 95% CI = 0.18 to 0.93, P = .032) and SCCs (RR = 0.42, 95% CI = 0.19 to 0.93, P = .032). Serious and cardiovascular adverse events were similar in the two groups.ConclusionsCelecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers.